title: New treatment for IgA nephropathy: enteric budesonide targeted to the ileocecal region ameliorates proteinuria.
abstract: BACKGROUND
  Systemic corticosteroid treatment has been shown to exert some protection against renal deterioration in IgA nephropathy (IgAN) but is not commonly recommended for long-term use due to the well-known systemic side effects. In this study, we investigated the efficacy and safety of a new enteric formulation of the locally acting glucocorticoid budesonide (Nefecon®), designed to release the active compound in the ileocecal region. The primary objective was to evaluate the efficacy of targeted release budesonide on albuminuria.
  
  
  METHODS
  Budesonide 8 mg/day was given to 16 patients with IgAN for 6 months, followed by a 3-month follow-up period. The efficacy was measured as change in 24-h urine albumin excretion, serum creatinine and estimated glomerular filtration rate (eGFR).
  
  
  RESULTS
  The median relative reduction in urinary albumin excretion was 23% during the treatment period (interquartile range: -0.36 to -0.04, P = 0.04) with pretreatment values ranging from 0.3 to 6 g/24 h (median: 1.5 g/24 h). The median reduction in urine albumin peaked at 40% (interquartile range: -0.58 to -0.15) 2 months after treatment discontinuation. Serum creatinine was reduced by 6% (interquartile range: -0.12 to -0.02; P = 0.003), and eGFR [Modification of Diet in Renal Disease (MDRD)] increased ∼8% (interquartile range: 0.02-0.16, P = 0.003) during treatment. No major corticosteroid-related side effects were observed.
  
  
  CONCLUSIONS
  In the present pilot study, enteric budesonide targeted to the ileocecal region had a significant effect on urine albumin excretion, accompanied by a minor reduction of serum creatinine and a modest increase of eGFR calculated by the MDRD equation, while eGFR calculated from Cockcroft-Gault equation and cystatin C was not changed. Enteric budesonide may represent a new treatment of IgAN warranting further investigation.
authors.affiliation: Department of Medical Sciences, Division of Nephrology, Uppsala University Hospital, University of Uppsala, Uppsala, Sweden. hilde.smerud@medsci.uu.se
authors.forename: Hilde Kloster
authors.initials: HK
authors.lastname: Smerud
authors.forename: Peter
authors.initials: P
authors.lastname: Bárány
authors.forename: Karin
authors.initials: K
authors.lastname: Lindström
authors.forename: Anders
authors.initials: A
authors.lastname: Fernström
authors.forename: Anna
authors.initials: A
authors.lastname: Sandell
authors.forename: Peter
authors.initials: P
authors.lastname: Påhlsson
authors.forename: Bengt
authors.initials: B
authors.lastname: Fellström
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000517:prevention & control*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D019819:Budesonide / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000188:drug therapy*; D006801:Humans; D007080:Ileocecal Valve; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011379:Prognosis; D013608:Tablets, Enteric-Coated; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D013608:Tablets, Enteric-Coated; D019819:Budesonide